tbuckley/cabot-search huggingface dataset:
Abstract A025: Agency of the Cell: Convergence between Origin of Life, Evolution, Cognition and Cancer
Authors: Perry S. Marshall
Journal: Cancer Research (2022)

Abstract All cells exhibit agency and evolve purposefully. This is why cancer has outwitted doctors for 100 years and why Stage 3-4 patients are no better in 2022 than in 1930. Evolution was presumed to be random and purposeless, yet all cells possess cognition (Shapiro 2020). Cell behavior is normally algorithmic, but uniquely responds to novel situations. This is what makes evolution (and cancer) possible. Cognition—sensing and responding to the environment—is the unifying principle behind the genetic code, origin of life, evolution, consciousness, artificial intelligence, and cancer. Thus the central question in biology is: What is the nature and origin of cognition? A solution to the origin of the genetic code, for which the presenter’s organization offers a $10 million prize (announced at the Royal Society in 2019) is an unsolved cognition problem. This choice is a non-deterministic action of a free agent with sensory capacity and memory. It is not computable from prior states. As well as reading and reacting to its environment, it anticipates future threats, chooses goals and reasons inductively. Computers do none of these things. This new model explains the futility of reducing cancer to a single random or algorithmic component, and suggests we should treat cancer as an autonomous purposeful agent with unique identity and capacity to choose. Citation Format: Perry S. Marshall. Agency of the Cell: Convergence between Origin of Life, Evolution, Cognition and Cancer [abstract]. In: Proceedings of the AACR Special Conference on the Evolutionary Dynamics in Carcinogenesis and Response to Therapy; 2022 Mar 14-17. Philadelphia (PA): AACR; Cancer Res 2022;82(10 Suppl):Abstract nr A025.
Errors in Byline
Authors: Chana Weinstock, Anup Amatya, Julia Beaver
Journal: JAMA Oncology (2022)

Osama E. Rahma, MD; Greg Yothers, PhD; Theodore S. Hong, MD; Marcia M. Russell, MD; Y. Nancy You, MD; William Parker, MS; Samuel A. Jacobs, MD; Linda H. Colangelo, MS; Peter C. Lucas, MD, PhD; Marc J. Gollub, MD; William A. Hall, MD; Lisa A. Kachnic, MD; Namrata Vijayvergia, MD; Mark A. O’Rourke, MD; Bryan A. Faller, MD; Richard K. Valicenti, MD; Tracey E. Schefter, MD; Sagila George, MD; Radhika Kainthla, MD; Philip J. Stella, MD; Elin Sigurdson, MD; Norman Wolmark, MD; Thomas J. George, MD
RNA modification mapping with JACUSA2
Authors: Michael Piechotta, Isabel S. Naarmann-de Vries, Qi Wang, Janine Altmüller, Christoph Dieterich
Journal: Genome biology (2022)

Several high-throughput antibody-free methods for RNA modification detection from sequencing data have been developed. We present JACUSA2 as a versatile software solution and comprehensive analysis framework for RNA modification detection assays that are based on either the Illumina or Nanopore platform. Importantly, JACUSA2 can integrate information from multiple experiments, such as replicates and different conditions, and different library types, such as first- or second-strand cDNA libraries. We demonstrate its utility, showing analysis workflows for N6-methyladenosine (m6A) and pseudouridine (Ψ) detection on Illumina and Nanopore sequencing data sets. Our software and its R helper package are available as open source solutions.
Homologous or heterogenous vaccination boosters enhance neutralizing activities against SARS‐CoV‐2 Omicron BA.1 variant
Authors: Zhongcheng Zhou, Peng Du, Ning Li, Xinxin Xiong, Shengjun Tang, Qinjin Dai, Taorui Wang, Meixing Yu, Miao Man, Kelvin Lam, Daniel T. Baptista‐Hon, Wa Hou Tai, Olivia Monteiro, Weng Sam Ng, Un Man Lee, Zhihai Liu, Kang Zhang, Gen Li
Journal: MedComm (2022)

The SARS-CoV-2 Omicron BA.1 variant of concern contains more than 30 mutations in the spike protein, with half of these mutations localized in the receptor-binding domain (RBD). Emerging evidence suggests that these large number of mutations impact the neutralizing efficacy of vaccines and monoclonal antibodies. We investigated the relative contributions of spike protein and RBD mutations in Omicron BA.1 variants on infectivity, cell-cell fusion, and their sensitivity to neutralization by monoclonal antibodies or vaccinated sera from individuals who received homologous (CoronaVac, SinoPharm) or heterologous (CoronaVac-BNT162b2, BioNTech) and nonhuman primates that received a recombinant RBD protein vaccine. Our data overall reveal that the mutations in the spike protein reduced infectivity and cell-cell fusion compared to the D614G variant. The impaired infectivity and cell-cell fusion were dependent on non-RBD mutations. We also find reduced sensitivity to neutralization by monoclonal antibodies and vaccinated sera. However, our results also show that nonhuman primates receiving a recombinant RBD protein vaccine show substantial neutralization activity. Our study sheds light on the molecular differences in neutralizing antibody escape by the Omicron BA.1 variant, and highlights the promise of recombinant RBD vaccines in neutralizing the threat posed by the Omicron BA.1 variant.
Additive manufacturing in respiratory sciences – Current applications and future prospects
Authors: Simon Bock, Thomas Rades, Jukka Rantanen, Regina Scherließ
Journal: Advanced Drug Delivery Reviews (2022)

Additive Manufacturing (AM) comprises a variety of techniques that enable fabrication of customised objects with specific attributes. The versatility of AM procedures and constant technological improvements allow for their application in the development of medicinal products and medical devices. This review provides an overview of AM applications related to respiratory sciences. For this purpose, both fields of research are briefly introduced and the potential benefits of integrating AM to respiratory sciences at different levels of pharmaceutical development are highlighted. Tailored manufacturing of microstructures as a particle design approach in respiratory drug delivery will be discussed. At the dosage form level, we exemplify AM as an important link in the iterative loop of data driven inhaler design, rapid prototyping and in vitro testing. This review also presents the application of bioprinting in the respiratory field for design of biorelevant in vitro cellular models, followed by an overview of AM-related processes in preventive and therapeutic care. Finally, this review discusses future prospects of AM as a component in a digital health environment.
Risk of intracranial hemorrhage with direct oral anticoagulants vs low molecular weight heparin in glioblastoma: A retrospective cohort study
Authors: Lauren Reed-Guy, Arati S Desai, Richard E Phillips, Desiree Croteau, Karen Albright, Meghan O’Neill, Steven Brem, Donald M O’Rourke, Nduka M Amankulor, Stephen J Bagley
Journal: Neuro-Oncology (2022)

Glioblastoma (GBM) is associated with a high incidence of venous thromboembolism (VTE), but there are little data to guide anticoagulation in patients with GBM, in whom the risks of VTE must be balanced against the risk of intracranial hemorrhage (ICH).We performed a single-institution retrospective cohort study of patients with GBM diagnosed with VTE from 2014 to 2021 who were treated with low molecular weight heparin (LMWH) or a direct oral anticoagulant (DOAC). The incidence of ICH was compared between the LMWH and DOAC groups. The primary outcome was clinically relevant ICH within the first 30 days of anticoagulation, defined as any ICH that was fatal, symptomatic, required surgical intervention, and/or led to cessation of anticoagulation. Secondary outcomes included clinically relevant ICH within 6 months, fatal ICH within 30 days and 6 months, and any bleeding within 30 days and 6 months.One hundred twenty-one patients were identified in the cohort for 30-day outcome analyses (DOAC, n = 33; LMWH, n = 88). For 6-month outcome analyses, the cohort included only patients who were maintained on their initial anticoagulant (DOAC, n = 32; LMWH, n = 75). The incidence of clinically relevant ICH at 30 days was 0% in the DOAC group and 9% in the LMWH group (P = .11). The cumulative incidence of clinically relevant ICH at 6 months was 0% in the DOAC group and 24% in the LMWH group (P = .001), with 4 fatal ICHs in the LMWH group.DOACs are associated with a lower incidence of clinically relevant ICH in patients with GBM-associated VTE compared to LMWH.
The Effect of Filter Lifespan during Continuous Renal Replacement Therapy in Critically Ill Patients with Acute Kidney Injury on the Rate of New-Onset Infection: Analysis from the RICH Randomized Controlled Trial
Authors: Joachim Gerss, Melanie Meersch, Detlef Kindgen-Milles, Timo Brandenburger, Carsten Willam, John A. Kellum, Alexander Zarbock
Journal: American Journal of Respiratory and Critical Care Medicine (2022)

"The Effect of Filter Lifespan during Continuous Renal Replacement Therapy in Critically Ill Patients with Acute Kidney Injury on the Rate of New-Onset Infection: Analysis from the RICH Randomized Controlled Trial." American Journal of Respiratory and Critical Care Medicine, 206(4), pp. 511–514
Targeting CISH enhances natural cytotoxicity receptor signaling and reduces NK cell exhaustion to improve solid tumor immunity
Authors: Pierre-Louis Bernard, Rebecca Delconte, Sonia Pastor, Vladimir Laletin, Cathy Costa Da Silva, Armelle Goubard, Emmanuelle Josselin, Rémy Castellano, Adrien Krug, Julien Vernerey, Raynier Devillier, Daniel Olive, Els Verhoeyen, Eric Vivier, Nicholas D Huntington, Jacques Nunes, Geoffrey Guittard
Journal: Journal for ImmunoTherapy of Cancer (2022)

The success and limitations of current immunotherapies have pushed research toward the development of alternative approaches and the possibility to manipulate other cytotoxic immune cells such as natural killer (NK) cells. Here, we targeted an intracellular inhibiting protein 'cytokine inducible SH2-containing protein' (CISH) in NK cells to evaluate the impact on their functions and antitumor properties.To further understand CISH functions in NK cells, we developed a conditional Cish-deficient mouse model in NK cells (Cishfl/flNcr1Ki/+ ). NK cells cytokine expression, signaling and cytotoxicity has been evaluated in vitro. Using intravenous injection of B16F10 melanoma cell line and EO711 triple negative breast cancer cell line, metastasis evaluation was performed. Then, orthotopic implantation of breast tumors was performed and tumor growth was followed using bioluminescence. Infiltration and phenotype of NK cells in the tumor was evaluated. Finally, we targeted CISH in human NK-92 or primary NK cells, using a technology combining the CRISPR(i)-dCas9 tool with a new lentiviral pseudotype. We then tested human NK cells functions.In Cishfl/flNcr1Ki/+ mice, we detected no developmental or homeostatic difference in NK cells. Global gene expression of Cishfl/flNcr1Ki/+ NK cells compared with Cish+/+Ncr1Ki/+ NK cells revealed upregulation of pathways and genes associated with NK cell cycling and activation. We show that CISH does not only regulate interleukin-15 (IL-15) signaling pathways but also natural cytotoxicity receptors (NCR) pathways, triggering CISH protein expression. Primed Cishfl/flNcr1Ki/+ NK cells display increased activation upon NCR stimulation. Cishfl/flNcr1Ki/+ NK cells display lower activation thresholds and Cishfl/flNcr1Ki/+ mice are more resistant to tumor metastasis and to primary breast cancer growth. CISH deletion favors NK cell accumulation to the primary tumor, optimizes NK cell killing properties and decreases TIGIT immune checkpoint receptor expression, limiting NK cell exhaustion. Finally, using CRISPRi, we then targeted CISH in human NK-92 or primary NK cells. In human NK cells, CISH deletion also favors NCR signaling and antitumor functions.This study represents a crucial step in the mechanistic understanding and safety of Cish targeting to unleash NK cell antitumor function in solid tumors. Our results validate CISH as an emerging therapeutic target to enhance NK cell immunotherapy.
Robotic Surgery for Bladder Cancer
Authors: Avinash Maganty, Lindsey A. Herrel, Brent K. Hollenbeck
Journal: JAMA (2022)

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Eculizumab impairs killing of Neisseria meningitidis serogroup B in atypical hemolytic uremic syndrome patients vaccinated with MenB-4C
Authors: Bryan van den Broek, Michiel van der Flier, Nicole C.A.J. van de Kar, Jack F.M. Wetzels, Marien I. de Jonge, Ronald de Groot, Kioa L. Wijnsma, Jeroen D. Langereis
Journal: Kidney International (2022)
Myxovirus resistance protein A for discriminating between viral and bacterial lower respiratory tract infections in children – The TREND study
Authors: Samuel Rhedin, Annika Eklundh, Malin Ryd-Rinder, Ville Peltola, Matti Waris, Jesper Gantelius, Magnus Lindh, Maria Andersson, Giulia Gaudenzi, Andreas Mårtensson, Pontus Naucler, Tobias Alfvén
Journal: Clinical Microbiology and Infection (2022)

Discriminating between viral and bacterial lower respiratory tract infection (LRTI) in children is challenging, leading to an excessive use of antibiotics. Myxovirus resistance protein A (MxA) is a promising biomarker for viral infections. The primary aim of the study was to assess differences in blood MxA levels between children with viral and bacterial LRTI. Secondary aims were to assess differences in blood MxA levels between children with viral LRTI and asymptomatic controls and to assess MxA levels in relation to different respiratory viruses.Children with LRTI were enrolled as cases at Sachs' Children and Youth Hospital, Stockholm, Sweden. Nasopharyngeal aspirates and blood samples for analysis of viral PCR, MxA, and C-reactive protein were systematically collected from all study subjects in addition to standard laboratory/radiology assessment. Aetiology was defined according to an algorithm based on laboratory and radiological findings. Asymptomatic children with minor surgical disease were enrolled as controls.MxA levels were higher in children with viral LRTI (n = 242) as compared to both bacterial (n = 5) LRTI (p <0.01, area under the curve (AUC) 0.90, 95% CI: 0.81 to 0.99), and controls (AUC 0.92, 95% CI: 0.88 to 0.95). In the subgroup of children with pneumonia diagnosis, a cutoff of MxA 430 μg/l discriminated between viral (n = 29) and bacterial (n = 4) aetiology with 93% (95% CI: 78-99%) sensitivity and 100% (95% CI: 51-100%) specificity (AUC 0.98, 95% CI: 0.94 to 1.00). The highest MxA levels were seen in cases PCR positive for influenza (median MxA 1699 μg/l, interquartile range: 732 to 2996) and respiratory syncytial virus (median MxA 1115 μg/l, interquartile range: 679 to 2489).MxA accurately discriminated between viral and bacterial aetiology in children with LRTI, particularly in the group of children with pneumonia diagnosis, but the number of children with bacterial LRTI was low.
External Validation of Three Available Grading Systems for Medullary Thyroid Carcinoma in a Single Institution Cohort
Authors: Elena Vissio, Francesca Maletta, Jessica Fissore, Simona Osella Abate, Francesca Retta, Maria Pia Brizzi, Alessandro Piovesan, Ruth Rossetto Giaccherino, Marco Volante, Mauro Papotti
Journal: Endocrine Pathology (2022)
How should we understand “bias” as a thick concept in recruitment discrimination studies?
Authors: Päivi Seppälä
Journal: Behavioral and Brain Sciences (2022)

Abstract Cesario criticizes the experimental design of studies of bias by claiming that acting on stereotypes in the experimental situation might not be an “error” from a Bayesian perspective. However, social psychologists might have an ethical reason to label the observed decision-maker biases as “erroneous.” Decision-making can be considered as “biased” and “erroneous,” because it reflects illegal and morally condemnable discrimination.
Rising incidence and prevalence of systemic lupus erythematosus: a population-based study over four decades
Authors: Alí Duarte-García, Mehmet Hocaoglu, Maria Valenzuela-Almada, Shirley-Ann Osei-Onomah, Jesse Y Dabit, Alain Sanchez-Rodriguez, Stephanie Q Duong, Rachel E Giblon, Hannah E Langenfeld, Graciela S Alarcón, Charles G Helmick, Cynthia S Crowson
Journal: Annals of the Rheumatic Diseases (2022)

Objectives To determine the trends in incidence, prevalence and mortality of systemic lupus erythematosus (SLE) in a US population over four decades. Methods We identified all the patients with SLE in Olmsted County, Minnesota who fulfilled the European Alliance of Associations for Rheumatology (EULAR)/American College of Rheumatology (ACR) criteria for SLE during 1976–2018. Age-specific and sex-specific incidence and prevalence rates were adjusted to the standard 2000 projected US population. The EULAR/ACR score was used as a proxy for disease severity. Standardised mortality ratio (SMR) was estimated. Results There were 188 incident SLE cases in 1976–2018 (mean age 46.3±SD 16.9; 83% women). Overall age-adjusted and sex-adjusted annual SLE incidence per 100 000 population was 4.77 (95% CI 4.09 to 5.46). Incidence was higher in women (7.58) than men (1.89). The incidence rate increased from 3.32 during 1976–1988 to 6.44 during 2009–2018. Incidence rates were higher among the racial and ethnic minority populations than non-Hispanic whites. The EULAR/ACR score did not change significantly over time. Overall prevalence increased from 30.6 in 1985 to 97.4 in 2015. During the study period, there was no improvement in SMR over time (p=0.31). Conclusions The incidence and prevalence of SLE are increasing in this US population. The increase in incidence may be at least partially explained by the rising ethnic/racial diversity of the population. There was no evidence that the severity of SLE has changed over time. The survival gap between SLE and the general population remains unchanged. As the US population grows more diverse, we might continue to see an increase in the incidence of SLE.
Paired primary and metastatic lesions of patients with ipilimumab-treated melanoma: high variation in lymphocyte infiltration and HLA-ABC expression whereas tumor mutational load is similar and correlates with clinical outcome
Authors: Mark A J Gorris, Lieke L van der Woude, Leonie I Kroeze, Kalijn Bol, Kiek Verrijp, Avital L Amir, Jelena Meek, Johannes Textor, Carl G Figdor, I Jolanda M de Vries
Journal: Journal for ImmunoTherapy of Cancer (2022)

Background Immune checkpoint inhibitors (ICI) can lead to long-term responses in patients with metastatic melanoma. Still many patients with melanoma are intrinsically resistant or acquire secondary resistance. Previous studies have used primary or metastatic tumor tissue for biomarker assessment. Especially in melanoma, metastatic lesions are often present at different anatomical sites such as skin, lymph nodes, and visceral organs. The anatomical site may directly affect the tumor microenvironment (TME). To evaluate the impact of tumor evolution on the TME and on ICI treatment outcome, we directly compared paired primary and metastatic melanoma lesions for tumor mutational burden (TMB), HLA-ABC status, and tumor infiltrating lymphocytes (TILs) of patients that received ipilimumab. Methods TMB was analyzed by sequencing primary and metastatic melanoma lesions using the TruSight Oncology 500 assay. Tumor tissues were subjected to multiplex immunohistochemistry to assess HLA-ABC status and for the detection of TIL subsets (B cells, cytotoxic T cells, helper T cells, and regulatory T cells), by using a machine-learning algorithm. Results While we observed a very good agreement between TMB of matched primary and metastatic melanoma lesions (intraclass coefficient=0.921), such association was absent for HLA-ABC status, TIL density, and subsets thereof. Interestingly, analyses of different metastatic melanoma lesions within a single patient revealed that TIL density and composition agreed remarkably well, rejecting the hypothesis that the TME of different anatomical sites affects TIL infiltration. Similarly, the HLA-ABC status between different metastatic lesions within patients was also comparable. Furthermore, high TMB, of either primary or metastatic melanoma tissue, directly correlated with response to ipilimumab, whereas lymphocyte density or composition did not. Loss of HLA-ABC in the metastatic lesion correlated to a shorter progression-free survival on ipilimumab. Conclusions We confirm the link between TMB and HLA-ABC status and the response to ipilimumab-based immunotherapy in melanoma, but no correlation was found for TIL density, neither in primary nor metastatic lesions. Our finding that TMB between paired primary and metastatic melanoma lesions is highly stable, demonstrates its independency of the time point and location of acquisition. TIL and HLA-ABC status in metastatic lesions of different anatomical sites are highly similar within an individual patient.
Paving the way for phage therapy using novel drug delivery approaches
Authors: Thomas Briot, Camille Kolenda, Tristan Ferry, Mathieu Medina, Frederic Laurent, Gilles Leboucher, Fabrice Pirot
Journal: Journal of Controlled Release (2022)

Bacterial resistance against antibiotics is an emergent medical issue. The development of novel therapeutic approaches is urgently needed and, in this context, bacteriophages represent a promising strategy to fight multi resistant bacteria. However, for some applications, bacteriophages cannot be used without an appropriate drug delivery system which increases their stability or provides an adequate targeting to the site of infection. This review summarizes the main application routes for bacteriophages and presents the new delivery approaches designed to increase phage's activity. Clinical successes of these formulations are also highlighted. Globally, this work paves the way for the design and optimization of nano and micro delivery systems for phage therapy.
What should equity in global health research look like?
Authors: Manasi Kumar, Lukoye Atwoli, Rochelle A Burgess, Naoufel Gaddour, Keng Yen Huang, Lola Kola, Emily Mendenhall, Cyrus Mugo, Byamah B Mutamba, Noeline Nakasujja, Irene Njuguna, Angela Obasi, Inge Petersen, Rahul Shidhaye
Journal: The Lancet (2022)
Fighting over who dictates the nature of prejudice
Authors: Gordon Hodson
Journal: Behavioral and Brain Sciences (2022)

A growing trend, reflected in the target article, effectively shifts control of prejudice operationalization to align with right-leaning priorities (and away from disadvantaged groups' voices and social justice). The article would only be compelling if experiments misaligned with real-world findings, if experimenters ignored nuances and moderators, and if the call to consider the social context included the macro-level societal context.